VIP and PACAP: Neuropeptide modulators of CNS inflammation, injury, and repair

British Journal of Pharmacology

Volumn 169, Issue 3, 2013, Pages 512-523

  Waschek, J A ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

EAE; experimental autoimmune encephalomyelitis; inflammation; injury; multiple sclerosis; neurodegeneration; neuropeptides; PACAP; VIP

Indexed keywords

CYTOKINE; GAMMA INTERFERON; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE; TUMOR NECROSIS FACTOR ALPHA; VASOACTIVE INTESTINAL POLYPEPTIDE;

ALLERGIC ENCEPHALOMYELITIS; ANTIINFLAMMATORY ACTIVITY; ASTROCYTE; BINDING AFFINITY; BRAIN NERVE CELL; CELLULAR IMMUNITY; CENTRAL NERVOUS SYSTEM DISEASE; CYTOKINE PRODUCTION; DEGENERATIVE DISEASE; DRUG RECEPTOR BINDING; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; INFLAMMATORY CELL; MACROPHAGE; MICROGLIA; NERVE REGENERATION; NERVOUS SYSTEM INFLAMMATION; NERVOUS SYSTEM INJURY; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; TH1 CELL; TH17 CELL; TH2 CELL; UPREGULATION;

ANIMALS; BRAIN DISEASES; CENTRAL NERVOUS SYSTEM; HUMANS; LIGANDS; MODELS, BIOLOGICAL; PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE; RECEPTORS, PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE; RECEPTORS, VASOACTIVE INTESTINAL PEPTIDE; SIGNAL TRANSDUCTION; SPINAL CORD DISEASES; VASOACTIVE INTESTINAL PEPTIDE;

EID: 84877824732     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12181     Document Type: Review

References (117)

1. Abad C, Waschek JA, (2011). Immunomodulatory roles of VIP and PACAP in models of multiple sclerosis. Curr Pharm Des 17: 1025-1035.
2. Abad C, Martinez C, Leceta J, Juarranz MG, Delgado M, Gomariz RP, (2002). Pituitary adenylate-cyclase-activating polypeptide expression in the immune system. Neuroimmunomodulation 10: 177-186.
3. Abad C, Tan YV, Lopez R, Nobuta H, Dong H, Phan P, et al. (2010). Vasoactive intestinal peptide loss leads to impaired CNS parenchymal T-cell infiltration and resistance to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 107: 19555-19560.
4. Andersen O, Fahrenkrug J, Wikkelso C, Johansson BB, (1984). VIP in cerebrospinal fluid of patients with multiple sclerosis. Peptides 5: 435-437.
5. Armstrong BD, Hu Z, Abad C, Yamamoto M, Rodriguez WI, Cheng J, et al. (2003). Lymphocyte regulation of neuropeptide gene expression after neuronal injury. J Neurosci Res 74: 240-247.
6. Armstrong BD, Hu Z, Abad C, Yamamoto M, Rodriguez WI, Cheng J, et al. (2004). Induction of neuropeptide gene expression and blockade of retrograde transport in facial motor neurons following local peripheral nerve inflammation in severe combined immunodeficiency and BALB/C mice. Neuroscience 129: 93-99.
7. Armstrong BD, Abad C, Chhith S, Cheung-Lau G, Hajji OE, Nobuta H, et al. (2008). Impaired nerve regeneration and enhanced neuroinflammatory response in mice lacking pituitary adenylyl cyclase activating peptide. Neuroscience 151: 63-73.
8. Barrie AP, Clohessy AM, Buensuceso CS, Rogers MV, Allen JM, (1997). Pituitary adenylyl cyclase-activating peptide stimulates extracellular signal-regulated kinase 1 or 2 (ERK1/2) activity in a Ras-independent, mitogen-activated protein Kinase/ERK kinase 1 or 2-dependent manner in PC12 cells. J Biol Chem 272: 19666-19671.
9. Beaudet MM, Braas KM, May V, (1998). Pituitary adenylate cyclase activating polypeptide (PACAP) expression in sympathetic preganglionic projection neurons to the superior cervical ganglion. J Neurobiol 36: 325-336.
10. Belai A, Boulos PB, Robson T, Burnstock G, (1997). Neurochemical coding in the small intestine of patients with Crohn's disease. Gut 40: 767-774.
11. Bellinger DL, Lorton D, Horn L, Brouxhon S, Felten SY, Felten DL, (1997). Vasoactive intestinal polypeptide (VIP) innervation of rat spleen, thymus, and lymph nodes. Peptides 18: 1139-1149.
12. Bellinger DL, Millar BA, Perez S, Carter J, Wood C, ThyagaRajan S, et al. (2008). Sympathetic modulation of immunity: relevance to disease. Cell Immunol 252: 27-56.
13. Boyer L, Sidpra D, Jevon G, Buchan AM, Jacobson K, (2007). Differential responses of VIPergic and nitrergic neurons in paediatric patients with Crohn's disease. Auton Neurosci 134: 106-114.
14. Braas KM, Schutz KC, Bond JP, Vizzard MA, Girard BM, May V, (2007). Microarray analyses of pituitary adenylate cyclase activating polypeptide (PACAP)-regulated gene targets in sympathetic neurons. Peptides 28: 1856-1870.
15. Brenneman DE, (2007). Neuroprotection: a comparative view of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Peptides 28: 1720-1726.
16. Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC, (2006). CNS immune privilege: hiding in plain sight. Immunol Rev 213: 48-65.
17. Chen WH, Tzeng SF, (2005). Pituitary adenylate cyclase-activating polypeptide prevents cell death in the spinal cord with traumatic injury. Neurosci Lett 384: 117-121.
18. Chen Y, Samal B, Hamelink CR, Xiang CC, Chen Y, Chen M, et al. (2006). Neuroprotection by endogenous and exogenous PACAP following stroke. Regul Pept 137: 4-19.
19. Cheng A, Hou Y, Mattson MP, (2010). Mitochondria and neuroplasticity. ASN Neuro 2: e00045.
20. Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, Krainc D, (2006). Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 127: 59-69.
21. Dejda A, Sokolowska P, Nowak JZ, (2005). Neuroprotective potential of three neuropeptides PACAP, VIP and PHI. Pharmacol Rep 57: 307-320.
22. Dejda A, Jolivel V, Bourgault S, Seaborn T, Fournier A, Vaudry H, et al. (2008). Inhibitory effect of PACAP on caspase activity in neuronal apoptosis: a better understanding towards therapeutic applications in neurodegenerative diseases. J Mol Neurosci 36: 26-37.
23. Delgado M, Ganea D, (1999). Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit interleukin-12 transcription by regulating nuclear factor kappaB and Ets activation. J Biol Chem 274: 31930-31940.
24. Delgado M, Ganea D, (2000). Inhibition of IFN-gamma-induced janus kinase-1-STAT1 activation in macrophages by vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. J Immunol 165: 3051-3057.
25. Delgado M, Ganea D, (2001). Inhibition of endotoxin-induced macrophage chemokine production by vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide in vitro and in vivo. J Immunol 167: 966-975.
26. Delgado M, Munoz-Elias EJ, Gomariz RP, Ganea D, (1999a). Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide enhance IL-10 production by murine macrophages: in vitro and in vivo studies. J Immunol 162: 1707-1716.
27. Delgado M, Munoz-Elias EJ, Gomariz RP, Ganea D, (1999b). VIP and PACAP inhibit IL-12 production in LPS-stimulated macrophages. Subsequent effect on IFNgamma synthesis by T cells. J Neuroimmunol 96: 167-181.
28. Delgado M, Sun W, Leceta J, Ganea D, (1999c). VIP and PACAP differentially regulate the costimulatory activity of resting and activated macrophages through the modulation of B7.1 and B7.2 expression. J Immunol 163: 4213-4223.
29. Delgado M, Gomariz RP, Martinez C, Abad C, Leceta J, (2000). Anti-inflammatory properties of the type 1 and type 2 vasoactive intestinal peptide receptors: role in lethal endotoxic shock. Eur J Immunol 30: 3236-3246.
30. Delgado M, Pozo D, Ganea D, (2004a). The significance of vasoactive intestinal peptide in immunomodulation. Pharmacol Rev 56: 249-290.
31. Delgado M, Reduta A, Sharma V, Ganea D, (2004b). VIP/PACAP oppositely affects immature and mature dendritic cell expression of CD80/CD86 and the stimulatory activity for CD4(+) T cells. J Leukoc Biol 75: 1122-1130.
32. Emery AC, Eiden LE, (2012). Signaling through the neuropeptide GPCR PAC1 induces neuritogenesis via a single linear cAMP- and ERK-dependent pathway using a novel cAMP sensor. FASEB J 26: 3199-3211.
33. Falluel-Morel A, Aubert N, Vaudry D, Basille M, Fontaine M, Fournier A, et al. (2004). Opposite regulation of the mitochondrial apoptotic pathway by C2-ceramide and PACAP through a MAP-kinase-dependent mechanism in cerebellar granule cells. J Neurochem 91: 1231-1243.
34. Falluel-Morel A, Chafai M, Vaudry D, Basille M, Cazillis M, Aubert N, et al. (2007). The neuropeptide pituitary adenylate cyclase-activating polypeptide exerts anti-apoptotic and differentiating effects during neurogenesis: focus on cerebellar granule neurones and embryonic stem cells. J Neuroendocrinol 19: 321-327.
35. Falluel-Morel A, Aubert N, Vaudry D, Desfeux A, Allais A, Burel D, et al. (2008). Interactions of PACAP and ceramides in the control of granule cell apoptosis during cerebellar development. J Mol Neurosci 36: 8-15.
36. Fernandez-Martin A, Gonzalez-Rey E, Chorny A, Ganea D, Delgado M, (2006). Vasoactive intestinal peptide induces regulatory T cells during experimental autoimmune encephalomyelitis. Eur J Immunol 36: 318-326.
37. Gaytan F, Martinez-Fuentes AJ, Garcia-Navarro F, Vaudry H, Aguilar E, (1994). Pituitary adenylate cyclase-activating peptide (PACAP) immunolocalization in lymphoid tissues of the rat. Cell Tissue Res 276: 223-227.
38. Girard BM, Keller ET, Schutz KC, May V, Braas KM, (2004). Pituitary adenylate cyclase activating polypeptide and PAC1 receptor signaling increase Homer 1a expression in central and peripheral neurons. Regul Pept 123: 107-116.
39. Gomariz RP, Delgado M, Naranjo JR, Mellstrom B, Tormo A, Mata F, et al. (1993). VIP gene expression in rat thymus and spleen. Brain Behav Immun 7: 271-278.
40. Gonzalez-Rey E, Fernandez-Martin A, Chorny A, Martin J, Pozo D, Ganea D, et al. (2006). Therapeutic effect of vasoactive intestinal peptide on experimental autoimmune encephalomyelitis: down-regulation of inflammatory and autoimmune responses. Am J Pathol 168: 1179-1188.
41. Gray SL, Yamaguchi N, Vencova P, Sherwood NM, (2002). Temperature-sensitive phenotype in mice lacking pituitary adenylate cyclase-activating polypeptide. Endocrinology 143: 3946-3954.
42. Guirland C, Buck KB, Gibney JA, DiCicco-Bloom E, Zheng JQ, (2003). Direct cAMP signaling through G-protein-coupled receptors mediates growth cone attraction induced by pituitary adenylate cyclase-activating polypeptide. J Neurosci 23: 2274-2283.
43. Handschin C, Rhee J, Lin J, Tarr PT, Spiegelman BM, (2003). An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle. Proc Natl Acad Sci U S A 100: 7111-7116.
44. Harmar AJ, Arimura A, Gozes I, Journot L, Laburthe M, Pisegna JR, et al. (1998). International Union of Pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Pharmacol Rev 50: 265-270.
45. Harmar AJ, Fahrenkrug J, Gozes I, Laburthe M, May V, Pisegna JR, et al. (2012). Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol 166: 4-17.
46. Herrmann JE, Imura T, Song B, Qi J, Ao Y, Nguyen TK, et al. (2008). STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 28: 7231-7243.
47. Hondares E, Rosell M, Diaz-Delfin J, Olmos Y, Monsalve M, Iglesias R, et al. (2011). Peroxisome proliferator-activated receptor alpha (PPARalpha) induces PPARgamma coactivator 1alpha (PGC-1alpha) gene expression and contributes to thermogenic activation of brown fat: involvement of PRDM16. J Biol Chem 286: 43112-43122.
48. Jones EA, Conover J, Symes AJ, (2000). Identification of a novel gp130-responsive site in the vasoactive intestinal peptide cytokine response element. J Biol Chem 275: 36013-36020.
49. Juarranz Y, Gutierrez-Canas I, Santiago B, Carrion M, Pablos JL, Gomariz RP, (2008). Differential expression of vasoactive intestinal peptide and its functional receptors in human osteoarthritic and rheumatoid synovial fibroblasts. Arthritis Rheum 58: 1086-1095.
50. Kambe Y, Miyata A, (2012). Role of mitochondrial activation in PACAP dependent neurite outgrowth. J Mol Neurosci 48: 550-557.
51. Kato H, Ito A, Kawanokuchi J, Jin S, Mizuno T, Ojika K, et al. (2004). Pituitary adenylate cyclase-activating polypeptide (PACAP) ameliorates experimental autoimmune encephalomyelitis by suppressing the functions of antigen presenting cells. Mult Scler 10: 651-659.
52. Kim WK, Kan Y, Ganea D, Hart RP, Gozes I, Jonakait GM, (2000). Vasoactive intestinal peptide and pituitary adenylyl cyclase-activating polypeptide inhibit tumor necrosis factor-alpha production in injured spinal cord and in activated microglia via a cAMP-dependent pathway. J Neurosci 20: 3622-3630.
53. Koh SW, (1991). Signal transduction through the vasoactive intestinal peptide receptor stimulates phosphorylation of the tyrosine kinase pp60c-src. Biochem Biophys Res Commun 174: 452-458.
54. Korn T, Reddy J, Gao W, Bettelli E, Awasthi A, Petersen TR, et al. (2007). Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med 13: 423-431.
55. Leceta J, Martinez C, Delgado M, Garrido E, Gomariz RP, (1996). Expression of vasoactive intestinal peptide in lymphocytes: a possible endogenous role in the regulation of the immune system. Adv Neuroimmunol 6: 29-36.
56. Lelievre V, Pineau N, Du J, Wen CH, Nguyen T, Janet T, et al. (1998). Differential effects of peptide histidine isoleucine (PHI) and related peptides on stimulation and suppression of neuroblastoma cell proliferation. A novel VIP-independent action of PHI via MAP kinase. J Biol Chem 273: 19685-19690.
57. Levinson DF, Duan J, Oh S, Wang K, Sanders AR, Shi J, et al. (2011). Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications. Am J Psychiatry 168: 302-316.
58. Li JM, Southerland L, Hossain MS, Giver CR, Wang Y, Darlak K, et al. (2011). Absence of vasoactive intestinal peptide expression in hematopoietic cells enhances Th1 polarization and antiviral immunity in mice. J Immunol 187: 1057-1065.
59. Lu N, DiCicco-Bloom E, (1997). Pituitary adenylate cyclase-activating polypeptide is an autocrine inhibitor of mitosis in cultured cortical precursor cells. Proc Natl Acad Sci U S A 94: 3357-3362.
60. Martinez C, Delgado M, Abad C, Gomariz RP, Ganea D, Leceta J, (1999). Regulation of VIP production and secretion by murine lymphocytes. J Neuroimmunol 93: 126-138.
61. Martinez C, Abad C, Delgado M, Arranz A, Juarranz MG, Rodriguez-Henche N, et al. (2002). Anti-inflammatory role in septic shock of pituitary adenylate cyclase-activating polypeptide receptor. Proc Natl Acad Sci U S A 99: 1053-1058.
62. May V, Braas KM, (1995). Pituitary adenylate cyclase-activating polypeptide (PACAP) regulation of sympathetic neuron neuropeptide Y and catecholamine expression. J Neurochem 65: 978-987.
63. Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A, Jiang L, et al. (1989). Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun 164: 567-574.
64. Mohney RP, Siegel RE, Zigmond RE, (1994). Galanin and vasoactive intestinal peptide messenger RNAs increase following axotomy of adult sympathetic neurons. J Neurobiol 25: 108-118.
65. Moller K, Reimer M, Ekblad E, Hannibal J, Fahrenkrug J, Kanje M, et al. (1997). The effects of axotomy and preganglionic denervation on the expression of pituitary adenylate cyclase activating peptide (PACAP), galanin and PACAP type 1 receptors in the rat superior cervical ganglion. Brain Res 775: 166-182.
66. Monaghan TK, Mackenzie CJ, Plevin R, Lutz EM, (2008). PACAP-38 induces neuronal differentiation of human SH-SY5Y neuroblastoma cells via cAMP-mediated activation of ERK and p38 MAP kinases. J Neurochem 104: 74-88.
67. Murthy KS, Zhang KM, Jin JG, Grider JR, Makhlouf GM, (1993). VIP-mediated G protein-coupled Ca2+ influx activates a constitutive NOS in dispersed gastric muscle cells. Am J Physiol 265 (4 Pt 1): G660-G671.
68. Nakamachi T, Farkas J, Watanabe J, Ohtaki H, Dohi K, Arata S, et al. (2011). Role of PACAP in neural stem/progenitor cell and astrocyte-from neural development to neural repair. Curr Pharm Des 17: 973-984.
69. Nakamachi T, Matkovits A, Seki T, Shioda S, (2012a). Distribution and protective function of pituitary adenylate cyclase-activating polypeptide in the retina. Front Endocrinol 3: 1-10.
70. Nakamachi T, Tsuchida M, Kagami N, Yofu S, Wada Y, Hori M, et al. (2012b). IL-6 and PACAP receptor expression and localization after global brain ischemia in mice. J Mol Neurosci 48: 518-525.
71. Nance DM, Sanders VM, (2007). Autonomic innervation and regulation of the immune system (1987-2007). Brain Behav Immun 21: 736-745.
72. Nishimoto M, Miyakawa H, Wada K, Furuta A, (2011). Activation of the VIP/VPAC2 system induces reactive astrocytosis associated with increased expression of glutamate transporters. Brain Res 1383: 43-53.
73. Nobuta H, Ghiani CA, Paez PM, Spreuer V, Dong H, Korsak RA, et al. (2012). STAT3-Mediated astrogliosis protects myelin development in neonatal brain injury. Ann Neurol 72: 750-765.
74. Ohtaki H, Nakamachi T, Dohi K, Aizawa Y, Takaki A, Hodoyama K, et al. (2006). Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6. Proc Natl Acad Sci U S A 103: 7488-7493.
75. Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Ishii K, et al. (2006). Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med 12: 829-834.
76. Pettersson LM, Heine T, Verge VM, Sundler F, Danielsen N, (2004). PACAP mRNA is expressed in rat spinal cord neurons. J Comp Neurol 471: 85-96.
77. Puigserver P, Spiegelman BM, (2003). Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24: 78-90.
78. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM, (1998). A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92: 829-839.
79. Ransohoff RM, (2007). Microgliosis: the questions shape the answers. Nat Neurosci 10: 1507-1509.
80. Reglodi D, Lubics A, Tamas A, Szalontay L, Lengvari I, (2004). Pituitary adenylate cyclase activating polypeptide protects dopaminergic neurons and improves behavioral deficits in a rat model of Parkinson's disease. Behav Brain Res 151: 303-312.
81. Reglodi D, Kiss P, Lubics A, Tamas A, (2011). Review on the protective effects of PACAP in models of neurodegenerative diseases in vitro and in vivo. Curr Pharm Des 17: 962-972.
82. Rosas-Ballina M, Tracey KJ, (2009). The neurology of the immune system: neural reflexes regulate immunity. Neuron 64: 28-32.
83. Sanders VM, Kasprowicz DJ, Swanson-Mungerson MA, Podojil JR, Kohm AP, (2003). Adaptive immunity in mice lacking the beta(2)-adrenergic receptor. Brain Behav Immun 17: 55-67.
84. Seaborn T, Masmoudi-Kouli O, Fournier A, Vaudry H, Vaudry D, (2011). Protective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) against apoptosis. Curr Pharm Des 17: 204-214.
85. Sharpless NS, Thal LJ, Perlow MJ, Tabaddor K, Waltz JM, Shapiro KN, et al. (1984). Vasoactive intestinal peptide in cerebrospinal fluid. Peptides 5: 429-433.
86. Shioda S, Gozes I, (2011). VIP and PACAP: novel approaches to brain functions and neuroprotection. Curr Pharm Des 17: 961.
87. Skoglosa Y, Lewen A, Takei N, Hillered L, Lindholm D, (1999). Regulation of pituitary adenylate cyclase activating polypeptide and its receptor type 1 after traumatic brain injury: comparison with brain-derived neurotrophic factor and the induction of neuronal cell death. Neuroscience 90: 235-247.
88. Spengler D, Waeber C, Pantaloni C, Holsboer F, Bockaert J, Seeburg PH, et al. (1993). Differential signal transduction by five splice variants of the PACAP receptor. Nature 365: 170-175.
89. Ster J, De Bock F, Guerineau NC, Janossy A, Barrere-Lemaire S, Bos JL, et al. (2007). Exchange protein activated by cAMP (EPAC) mediates cAMP activation of p38 MAPK and modulation of Ca2+-dependent K+ channels in cerebellar neurons. Proc Natl Acad Sci U S A 104: 2519-2524.
90. Stetler RA, Gao Y, Zukin RS, Vosler PS, Zhang L, Zhang F, et al. (2010). Apurinic/apyrimidinic endonuclease APE1 is required for PACAP-induced neuroprotection against global cerebral ischemia. Proc Natl Acad Sci U S A 107: 3204-3209.
91. St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jager S, et al. (2006). Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127: 397-408.
92. Straub SG, Sharp GW, (1996). A wortmannin-sensitive signal transduction pathway is involved in the stimulation of insulin release by vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide. J Biol Chem 271: 1660-1668.
93. Stumm R, Kolodziej A, Prinz V, Endres M, Wu DF, Hollt V, (2007). Pituitary adenylate cyclase-activating polypeptide is up-regulated in cortical pyramidal cells after focal ischemia and protects neurons from mild hypoxic/ischemic damage. J Neurochem 103: 1666-1681.
94. Sun W, Hong J, Zang YC, Liu X, Zhang JZ, (2006). Altered expression of vasoactive intestinal peptide receptors in T lymphocytes and aberrant Th1 immunity in multiple sclerosis. Int Immunol 18: 1691-1700.
95. Symes AJ, Corpus L, Fink JS, (1995). Differences in nuclear signaling by leukemia inhibitory factor and interferon-gamma: the role of STAT proteins in regulating vasoactive intestinal peptide gene expression. J Neurochem 65: 1926-1933.
96. Tamas A, Zsombok A, Farkas O, Reglodi D, Pal J, Buki A, et al. (2006). Postinjury administration of pituitary adenylate cyclase activating polypeptide (PACAP) attenuates traumatically induced axonal injury in rats. J Neurotrauma 23: 686-695.
97. Tan YV, Abad C, Lopez R, Dong H, Liu S, Lee A, et al. (2009). Pituitary adenylyl cyclase-activating polypeptide is an intrinsic regulator of Treg abundance and protects against experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 106: 2012-2017.
98. Tanida M, Shintani N, Morita Y, Tsukiyama N, Hatanaka M, Hashimoto H, et al. (2010). Regulation of autonomic nerve activities by central pituitary adenylate cyclase-activating polypeptide. Regul Pept 161: 73-80.
99. Thayer JF, Sternberg EM, (2010). Neural aspects of immunomodulation: focus on the vagus nerve. Brain Behav Immun 24: 1223-1228.
100. Tornwall J, Uusitalo H, Hukkanen M, Sorsa T, Konttinen YT, (1994). Distribution of vasoactive intestinal peptide (VIP) and its binding sites in labial salivary glands in Sjogren's syndrome and in normal controls. Clin Exp Rheumatol 12: 287-292.
101. Tracey KJ, (2009). Reflex control of immunity. Nat Rev Immunol 9: 418-428.
102. Tsuchikawa D, Nakamachi T, Tsuchida M, Wada Y, Hori M, Farkas J, et al. (2012). Neuroprotective effect of endogenous pituitary adenylate cyclase-activating polypeptide on spinal cord injury. J Mol Neurosci 48: 508-517.
103. Vacic V, McCarthy S, Malhotra D, Murray F, Chou HH, Peoples A, et al. (2011). Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. Nature 471: 499-503.
104. Vassiliou E, Jiang X, Delgado M, Ganea D, (2001). TH2 lymphocytes secrete functional VIP upon antigen stimulation. Arch Physiol Biochem 109: 365-368.
105. Vaudry D, Falluel-Morel A, Bourgault S, Basille M, Burel D, Wurtz O, et al. (2009). Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol Rev 61: 283-357.
106. Villalba M, Bockaert J, Journot L, (1997). Pituitary adenylate cyclase-activating polypeptide (PACAP-38) protects cerebellar granule neurons from apoptosis by activating the mitogen-activated protein kinase (MAP kinase) pathway. J Neurosci 17: 83-90.
107. Wainwright DA, Xin J, Sanders VM, Jones KJ, (2008). Differential actions of pituitary adenylyl cyclase-activating polypeptide and interferon gamma on Th2- and Th1-associated chemokine expression in cultured murine microglia. J Neurodegener Regen 1: 31-34.
108. Wang G, Pan J, Tan YY, Sun XK, Zhang YF, Zhou HY, et al. (2008). Neuroprotective effects of PACAP27 in mice model of Parkinson's disease involved in the modulation of K(ATP) subunits and D2 receptors in the striatum. Neuropeptides 42: 267-276.
109. Waschek JA, (1995). Vasoactive intestinal peptide: an important trophic factor and developmental regulator? Dev Neurosci 17: 1-7.
110. Waschek JA, (2002). Multiple actions of pituitary adenylyl cyclase activating peptide in nervous system development and regeneration. Dev Neurosci 24: 14-23.
111. Waschek JA, Dicicco-Bloom EM, Lelievre V, Zhou X, Hu Z, (2000). PACAP action in nervous system development, regeneration, and neuroblastoma cell proliferation. Ann N Y Acad Sci 921: 129-136.
112. Yadav M, Goetzl EJ, (2008). Vasoactive intestinal peptide-mediated Th17 differentiation: an expanding spectrum of vasoactive intestinal peptide effects in immunity and autoimmunity. Ann N Y Acad Sci 1144: 83-89.
113. Zaben M, Sheward WJ, Shtaya A, Abbosh C, Harmar AJ, Pringle AK, et al. (2009). The neurotransmitter VIP expands the pool of symmetrically dividing postnatal dentate gyrus precursors via VPAC2 receptors or directs them toward a neuronal fate via VPAC1 receptors. Stem Cells 27: 2539-2551.
114. Zhang Q, Shi TJ, Ji RR, Zhang YZ, Sundler F, Hannibal J, et al. (1995). Expression of pituitary adenylate cyclase-activating polypeptide in dorsal root ganglia following axotomy: time course and coexistence. Brain Res 705: 149-158.
115. Zhang Y, Danielsen N, Sundler F, Mulder H, (1998). Pituitary adenylate cyclase-activating peptide is upregulated in sensory neurons by inflammation. Neuroreport 9: 2833-2836.
116. Zhou X, Rodriguez WI, Casillas RA, Ma V, Tam J, Hu Z, et al. (1999). Axotomy-induced changes in pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP receptor gene expression in the adult rat facial motor nucleus. J Neurosci Res 57: 953-961.
117. Zigmond RE, (2011). gp130 cytokines are positive signals triggering changes in gene expression and axon outgrowth in peripheral neurons following injury. Front Mol Neurosci 4: 1-18.